Crystal structure and Hirshfeld surface analysis of 4-(4-chloro­phen­yl)-5-methyl-3-{4-[(2-methyl­phen­yl)meth­oxy]phen­yl}-1,2-oxazole

Aydin, A.; Akkurt, M.; Turanli, S.; Lengerli, D.; Banoglu, E.; Ozcelik, N.D.

doi:10.1107/S2056989021002383

research communications

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 77| Part 4| April 2021| Pages 346-350

https://doi.org/10.1107/S2056989021002383

Open

access

Crystal structure and Hirshfeld surface analysis of 4-(4-chlorophenyl)-5-methyl-3-{4-[(2-methylphenyl)methoxy]phenyl}-1,2-oxazole

Abdullah Aydin,^a ^* Mehmet Akkurt,^b Sumeyye Turanli,^c Deniz Lengerli,^c Erden Banoglu ^c and Nefise Dilek Ozcelik ^d

^aDepartment of Mathematics and Science Education, Faculty of Education, Kastamonu University, 37200 Kastamonu, Turkey, ^bDepartment of Physics, Faculty of Sciences, Erciyes University, 38039 Kayseri, Turkey, ^cDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey, and ^dDepartment of Physics, Faculty of Arts and Sciences, Aksaray University, 68100 Aksaray, Turkey
^*Correspondence e-mail: aaydin@kastamonu.edu.tr

Edited by A. V. Yatsenko, Moscow State University, Russia (Received 17 February 2021; accepted 2 March 2021; online 5 March 2021)

In the title compound, C₂₄H₂₀ClNO₂, the mean planes of 4-chlorophenyl, 2-methylphenyl and phenylene rings make dihedral angles of 62.8 (2), 65.1 (3) and 15.1 (2)°, respectively, with the 5-methyl-1,2-oxazole ring. In the crystal, molecules are linked by intermolecular C—H⋯N, C—H⋯Cl, C—H⋯π contacts and π–π stacking interactions between the phenylene groups. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H⋯H (48.7%), H⋯C/C⋯H (22.2%), Cl⋯H/H⋯Cl (8.8%), H⋯O/O⋯H (8.2%) and H⋯N/N⋯H (5.1%) interactions.

Keywords: crystal structure; vicinal diaryl isoxazole; C—H⋯π interactions; Hirshfeld surface analysis.

CCDC reference: 2067449

1. Chemical context

Azoles are five-membered heterocycles that have been widely used as promising scaffolds in designing novel therapeutics, in particular anticancer agents (Ahmad et al., 2018 ). Among them, isoxazole, a five-membered heterocycle with consecutive nitrogen and oxygen atoms in the ring, is found to be a key structural component of many commercial drugs or drug candidates in clinical development (Barmade et al., 2016 ). Moreover, a number of vicinal diaryl isoxazoles reported in the literature exhibit anticancer and COX-2 inhibitory activities, such as luminesbip and valdexocib, respectively (Murumkar & Ghuge, 2018 ). One of the critical steps in rational drug design is obtaining knowledge of the structure of the new drug candidates, and single-crystal X-ray diffraction (SCXD) is one of the most powerful methods for gaining this fundamental information, which can be used to guide the drug-design studies in connection with other technologies such as pharmacophore model elaborations, 3D QSAR, docking, and de novo design. SCXD has thus become an essential tool for drug development to unambiguously determine the three-dimensional structures of molecules, which eventually paves the way for rapid development of new molecules (Wouters & Ooms, 2001 ). Moreover, during the drug-development process, another important issue lies in understanding the crystal packing of the active pharmaceutical ingredient (drug substance) for suitable formulation development. Since most drug molecules comprise solid dosage forms in the crystalline state, it is imperative to truly understand the relationships between the crystal structures and the solid properties of pharmaceutically active substances, which helps the best form of an active pharmaceutical ingredient to be chosen for development into a drug product (Aitipamula & Vangala, 2017 ). Based on the above and our continuing interest in structural studies and biological applications of diaryl heterocycles (Banoglu et al., 2016 ; Çalışkan et al., 2011 ; Dündar et al., 2009 ; Eren et al., 2010 ; Ergun et al., 2010 ; Garscha et al., 2016 ; Levent et al., 2013 ; Pirol et al., 2014 ; Ünlü et al., 2007 ), we report herein the crystal structure and Hirshfeld surface analysis of the title compound.

2. Structural commentary

In the molecule of the title compound (Fig. 1), the mean planes of 4-chlorophenyl, 2-methylphenyl and phenylene rings form dihedral angles of 62.8 (2), 65.1 (3) and 15.1 (2)°, respectively, with respect to the 5-methyl-1,2-oxazole ring. The 4-chlorophenyl ring makes dihedral angles of 77.4 (3) and 66.38 (19)°, respectively, with the 2-methylphenyl and phenylene rings, while the dihedral angle between the 2-methylphenyl and phenylene rings is 80.0 (3)°. The C14—O2—C17—C18 torsion angle is 166.7 (4)°. The terminal 2-methylphenyl group is involved in intense thermal motion.

Figure 1
Molecular structure of the title compound with the atom-numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 30% probability level.

3. Supramolecular features

In the crystal, molecules are linked by intermolecular C—H⋯N, C—H⋯Cl and C—H⋯π contacts (Table 1, Fig. 2) and π–π interactions between inversion-related phenylene rings [intercentroid separation Cg3⋯Cg3(1 − x, 1 − y, 1 − z) = 3.958 (2) Å] (Fig. 3).

Table 1
Intermolecular contacts (Å, °)

Cg1, Cg2 and Cg3 are the centroids of the O1/N1/C2–C4, C5–C10 and C11–C16 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C17—H17A⋯N1ⁱ	0.97	2.68	3.395 (6)	131
C6—H6⋯Cg3ⁱⁱ	0.93	2.86	3.747 (5)	159
C19—H19⋯Cg1ⁱⁱⁱ	0.93	2.77	3.614 (6)	151
C8—Cl1⋯Cg2^iv	1.75 (1)	3.37 (1)	5.034 (4)	159 (1)
Symmetry codes: (i) x, y, z+1; (ii) ; (iii) ; (iv) $[x, -y-{\script{1\over 2}}, z-{\script{1\over 2}}]$ .

Figure 2
A view of the C—H⋯N and C—H⋯π interactions in the unit cell of the title compound. Dashed lines show short intermolecular contacts.

Figure 3
A view of the C—H⋯N and C—H⋯π and π–π interactions in the unit cell of the title compound. Dashed lines show short intermolecular contacts.

4. Hirshfeld surface analysis

Hirshfeld surface analysis (Hirshfeld, 1977 ; Spackman & Jayatilaka, 2009 ) of the title compound was carried out to investigate the location of atoms with potential to form hydrogen bonds and other intermolecular contacts, and the quantitative ratio of these interactions. Crystal Explorer17.5 (Turner et al., 2017 ) was used to generate the Hirshfeld surfaces and two-dimensional fingerprint plots (Rohl et al., 2008 ). The Hirshfeld surfaces were generated using a standard (high) surface resolution with the three-dimensional d_norm surfaces mapped over a fixed colour scale of −0.0800 (red) to 1.5787 Å (blue) (Fig. 4).

Figure 4
The Hirshfeld surface of the title compound mapped with d_norm.

The red points, which represent closer contacts and negative d_norm values on the surface, correspond to the C—H⋯N (C17—H17A⋯N1), C—H⋯Cl (C8—Cl1⋯H1C—C1) and C—H⋯π (C6—H6⋯phenylene) interactions (Table 2). Except for the red spots, the overall surface mapped over d_norm is white and blue, indicating that the distances between the contact atoms in intermolecular contacts are nearly the same as the sum of their van der Waals radii or longer.

Table 2
Summary of selected van der Waals contacts (Å) involving H atoms in the title compound

Contact	Distance	Symmetry operation
Cl1⋯H1C	3.04	x, $[{1\over 2}]$ − y, $[{1\over 2}]$ + z
N1⋯H17A	2.68	x, y, −1 + z
H1A⋯O1	2.74	2 − x, 1 − y, −z
H10⋯O2	2.72	1 − x, 1 − y, 1 − z
H6⋯C11	2.80	2 − x, 1 − y, 1 − z
H9⋯C21	2.94	1 − x, − $[{1\over 2}]$ + y, $[{3\over 2}]$ − z
H20⋯C9	3.05	1 − x, 1 − y, 2 − z
H22⋯H24C	2.48	x, $[{1\over 2}]$ − y, − $[{1\over 2}]$ + z

The shape-index of the Hirshfeld surface is a tool for visualizing the π–π stacking by the presence of adjacent red and blue triangles; if there are no such triangles, then there are no π–π interactions. The plot of the Hirshfeld surface mapped over shape-index clearly suggests that there are π–π interactions in the title compound (Fig. 5).

Figure 5
Hirshfeld surface of the title compound plotted over shape-index.

Fig. 6(a) shows the total two-dimensional fingerprint plot providing information on the major and minor percentage contributions of the interatomic contacts to the Hirshfeld surface of the title compound. The blue colour refers to the frequency of occurrence of the (d_i, d_e) pair and the grey colour is the outline of the full fingerprint (Zaini et al., 2019 ). The fingerprint plots (Fig. 6b) show that the H⋯H contacts clearly make the most significant contribution to the Hirshfeld surface (48.7%). The H⋯C/C⋯H, Cl⋯H/H⋯Cl, H⋯O/O⋯H and H⋯N/N⋯H contacts contribute 22.2, 8.8, 8.2 and 5.1%, respectively (Fig. 6c–f). The remaining weaker contacts are listed in Table 3.

Table 3
Percentage contributions of interatomic contacts to the Hirshfeld surface of the title compound

Contact	Percentage contribution
H⋯H	48.7
H⋯C/C⋯H	22.2
Cl⋯H/H⋯Cl	8.8
H⋯O/O⋯H	8.2
H⋯N/N⋯H	5.1
Cl⋯C/C⋯Cl	3.9
C⋯C	2.1
C⋯N/N⋯C	0.4
O⋯O	0.4
C⋯O/O⋯C	0.2

Figure 6
The total two-dimensional fingerprint plot (a) and the relative contributions of various interactions to the Hirshfeld surface: (b) H⋯H, (c) H⋯C/C⋯H, (d) Cl⋯H/H⋯Cl, (e) H⋯O/O⋯H and (f) H⋯N/N⋯H.

The large number of H⋯H, H⋯C/C⋯H, Cl⋯H/H⋯Cl, H⋯O/O⋯H and H⋯N/N⋯H interactions suggest that van der Waals interactions play the major roles in the crystal packing (Hathwar et al., 2015 ).

5. Database survey

The closest related 1,2-oxazole compounds containing a halogen atom, but with different substituents at the aromatic rings are: ethyl 3-(4-chlorophenyl)-5-[(E)-2- (dimethylamino)ethenyl]-1,2-oxazole-4- carboxylate [(I); Efimov et al., 2015 ], N-(2,4-difluorophenyl)-5-methyl-1,2-oxazole-4-carboxamide hemihydrate [(II); Yu et al., 2012 ] and N-(2,6-dichlorophenyl)-5-methyl-1,2-oxazole-4-carboxamide monohydrate [(III); Wang et al., 2011 ].

In compound (I), the asymmetric unit contains two molecules, A and B, with different conformations. In molecule A, the C=O group of the ester points away from the benzene ring [C—C—C=O = −170.8 (3)°], whereas in molecule B, it points back towards the benzene ring [C—C—C=O = 17.9 (4)°]. The dihedral angles between the oxazole and benzene rings are also somewhat different [46.26 (13) and 41.59 (13)° for molecules A and B, respectively]. Each molecule features an intramolecular C—H⋯O interaction, which closes an S(6) ring. In the crystal, the B molecules are linked into C(12) chains along the c-axis direction by weak C—H⋯Cl interactions. In the crystal of (II), the components are linked by O—H⋯N and N—H⋯O hydrogen bonds, where the water molecule acts as both an H-atom donor and an acceptor, into a tape along the a-axis direction with an R₄⁴(16) graph-set motif. The water molecule is located on a twofold rotation axis. In (III), the dihedral angle between the benzene and isoxazole rings is 59.10 (7)°. In the crystal, the components are linked by N—H⋯O and O—H⋯O hydrogen bonds into a three-dimensional network. The crystal structure is further stabilized by π-stacking interactions [intercentroid distance = 3.804 (2) Å].

6. Synthesis and crystallization

Step 1: To a solution of N-hydroxy-4-[(2-methylbenzyl)oxy]benzimidoyl chloride (275 mg, 1 mmol) in diethyl ether (6 ml) was added Et₃N (139.4 µL, 1 mmol). The resulting mixture was stirred for 2 h in an ice bath, and the precipitate formed was filtered off. The filtrate was evaporated under vacuum to obtain the arylnitriloxide intermediate.

Step 2: To a solution of NaH (60% in mineral oil, 64 mg, 1.6 mmol) in dry THF (4 ml), 4-chlorophenylacetone (168,6 mg, 1.0 mmol) was added dropwise, and stirred for 1 h under a nitrogen atmosphere in an ice bath. At the end of the period, the arylnitriloxide intermediate was dissolved in dry THF (4 ml), and was added to the reaction mixture, then stirred at room temperature overnight. Upon completion of the reaction, aqueous ammonium chloride solution was added, and the product was extracted with EtOAc (2 × 50 mL). The combined organic extracts were dried over anhydrous Na₂SO₄, filtered and evaporated to dryness. The crude product was purified by automated-flash chromatography on silica gel (12 g) eluting with a gradient of 0 to 40% EtOAc in hexane. The obtained pure product was recrystallized from methanol. Crystals for structural study were obtained by slow cooling of the solution, yield 77%, m.p. 387.2–388.6 K.

¹H NMR (400 MHz, CDCl₃): δ 2.29 (3H, s), 2.39 (3H, s), 5.07 (2H, s), 7.05 (2H, d, J = 8.4 Hz), 7.15–7.25 (5H, m), 7.27 (2H, d, J = 8.8 Hz), 7.38 (1H, d, J = 7.6 Hz), 7.47 (2H, d, J = 8.4 Hz).

¹³C NMR (100 MHz, CDCl₃): δ 11.21, 18.42, 67.98, 113.96, 114.97, 120.84, 125.77, 128.15, 128.59, 128.86, 129.43, 130.12, 131.44, 132.57, 134.58, 136.64, 159.49, 160.09, 166.93. HRMS (m/z): [M + H]⁺ calculated for C₂₄H₂₁ClNO₂: 390.1261; found: 390.1263.

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 4. H atoms were positioned geometrically (C—H = 0.93–0.97 Å) and refined as riding with U_iso(H) = 1.2U_eq(C) or 1.5U_eq(C-methyl). In the final refinement, three outliers (1 11 9, 2 16 7, $[\overline{1}]$ 19 6) were omitted.

Table 4
Experimental details

Crystal data
Chemical formula	C₂₄H₂₀ClNO₂
M_r	389.86
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	296
a, b, c (Å)	10.5733 (10), 22.848 (2), 8.7151 (9)
β (°)	101.477 (4)
V (Å³)	2063.3 (4)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.20
Crystal size (mm)	0.17 × 0.13 × 0.11

Data collection
Diffractometer	Bruker SMART BREEZE CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2007 )
T_min, T_max	0.598, 0.745
No. of measured, independent and observed [I > 2σ(I)] reflections	45630, 3840, 3030
R_int	0.064
(sin θ/λ)_max (Å⁻¹)	0.606

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.099, 0.187, 1.25
No. of reflections	3840
No. of parameters	255
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.29, −0.33
Computer programs: APEX2 and SAINT (Bruker, 2007), SHELXT2014/4 (Sheldrick, 2015a ), SHELXL2018/3 (Sheldrick, 2015b ), ORTEP-3 for Windows and WinGX (Farrugia, 2012 ) and PLATON (Spek, 2020 ).

Supporting information

CCDC reference: 2067449

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989021002383/yk2147sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989021002383/yk2147Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989021002383/yk2147Isup3.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXT2014/4 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: PLATON (Spek, 2020) and WinGX (Farrugia, 2012).

4-(4-Chlorophenyl)-5-methyl-3-{4-[(2-methylphenyl)methoxy]phenyl}-1,2-oxazole top

Crystal data top

C₂₄H₂₀ClNO₂	F(000) = 816
M_r = 389.86	D_x = 1.255 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 10.5733 (10) Å	Cell parameters from 9984 reflections
b = 22.848 (2) Å	θ = 2.9–26.1°
c = 8.7151 (9) Å	µ = 0.20 mm⁻¹
β = 101.477 (4)°	T = 296 K
V = 2063.3 (4) Å³	Block, colourless
Z = 4	0.17 × 0.13 × 0.11 mm

Data collection top

Bruker SMART BREEZE CCD diffractometer	3030 reflections with I > 2σ(I)
φ and ω scans	R_int = 0.064
Absorption correction: multi-scan (SADABS; Bruker, 2007)	θ_max = 25.5°, θ_min = 2.9°
T_min = 0.598, T_max = 0.745	h = −12→12
45630 measured reflections	k = −27→27
3840 independent reflections	l = −10→10

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.099	H-atom parameters constrained
wR(F²) = 0.187	w = 1/[σ²(F_o²) + (0.0303P)² + 3.1816P] where P = (F_o² + 2F_c²)/3
S = 1.25	(Δ/σ)_max < 0.001
3840 reflections	Δρ_max = 0.29 e Å⁻³
255 parameters	Δρ_min = −0.33 e Å⁻³

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.9916 (5)	0.3972 (2)	0.0798 (6)	0.0786 (15)
H1A	1.073792	0.414990	0.079720	0.118*
H1B	0.949677	0.388351	−0.025762	0.118*
H1C	1.003929	0.361730	0.140061	0.118*
C2	0.9100 (4)	0.43821 (19)	0.1503 (5)	0.0575 (11)
C3	0.8681 (4)	0.43905 (16)	0.2861 (4)	0.0445 (9)
C4	0.7911 (4)	0.49060 (16)	0.2788 (4)	0.0477 (9)
C5	0.8951 (3)	0.39390 (15)	0.4106 (4)	0.0399 (8)
C6	1.0198 (4)	0.38314 (18)	0.4902 (5)	0.0559 (11)
H6	1.087573	0.404533	0.464626	0.067*
C7	1.0458 (4)	0.34153 (19)	0.6061 (5)	0.0601 (11)
H7	1.129976	0.334858	0.658977	0.072*
C8	0.9461 (4)	0.31025 (16)	0.6423 (4)	0.0505 (10)
C9	0.8221 (4)	0.31897 (17)	0.5654 (4)	0.0513 (10)
H9	0.755403	0.296826	0.590784	0.062*
C10	0.7965 (4)	0.36096 (17)	0.4494 (4)	0.0474 (9)
H10	0.712000	0.367117	0.396865	0.057*
C11	0.7223 (4)	0.51653 (15)	0.3940 (4)	0.0434 (9)
C12	0.7465 (4)	0.50001 (17)	0.5498 (5)	0.0534 (10)
H12	0.804645	0.469849	0.582691	0.064*
C13	0.6866 (4)	0.52715 (17)	0.6581 (5)	0.0560 (11)
H13	0.703823	0.515063	0.762061	0.067*
C14	0.6014 (4)	0.57204 (18)	0.6108 (4)	0.0511 (10)
C15	0.5757 (4)	0.5890 (2)	0.4563 (5)	0.0638 (12)
H15	0.517749	0.619299	0.423717	0.077*
C16	0.6351 (4)	0.5615 (2)	0.3503 (5)	0.0604 (11)
H16	0.616425	0.573436	0.246158	0.072*
C17	0.5646 (5)	0.5876 (2)	0.8714 (5)	0.0726 (14)
H17A	0.656655	0.583009	0.909755	0.087*
H17B	0.522468	0.550907	0.885738	0.087*
C18	0.5135 (4)	0.6354 (2)	0.9591 (4)	0.0599 (12)
C19	0.4002 (5)	0.6258 (3)	1.0119 (6)	0.0900 (17)
H19	0.356626	0.590511	0.988715	0.108*
C20	0.3513 (7)	0.6669 (5)	1.0973 (8)	0.130 (3)
H20	0.275977	0.659313	1.133673	0.156*
C21	0.4116 (11)	0.7181 (4)	1.1287 (9)	0.136 (4)
H21	0.377369	0.746428	1.185453	0.163*
C22	0.5229 (9)	0.7290 (3)	1.0780 (8)	0.117 (3)
H22	0.563766	0.764957	1.100443	0.140*
C23	0.5775 (6)	0.6873 (3)	0.9926 (6)	0.0797 (15)
C24	0.7025 (7)	0.6991 (3)	0.9434 (8)	0.134 (3)
H24A	0.769778	0.676652	1.007418	0.200*
H24B	0.722625	0.739980	0.955410	0.200*
H24C	0.695494	0.688090	0.835677	0.200*
Cl1	0.97763 (16)	0.25691 (6)	0.78820 (15)	0.0889 (5)
N1	0.7874 (4)	0.51849 (16)	0.1458 (4)	0.0666 (10)
O1	0.8631 (3)	0.48497 (14)	0.0621 (3)	0.0709 (9)
O2	0.5395 (3)	0.60330 (14)	0.7082 (3)	0.0668 (9)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.092 (4)	0.084 (4)	0.071 (3)	0.014 (3)	0.042 (3)	0.013 (3)
C2	0.066 (3)	0.054 (2)	0.055 (2)	0.000 (2)	0.019 (2)	0.012 (2)
C3	0.049 (2)	0.043 (2)	0.041 (2)	−0.0046 (17)	0.0083 (17)	0.0078 (17)
C4	0.058 (2)	0.045 (2)	0.040 (2)	−0.0057 (18)	0.0081 (17)	0.0113 (17)
C5	0.049 (2)	0.0339 (18)	0.0374 (19)	−0.0043 (16)	0.0101 (16)	−0.0036 (15)
C6	0.051 (2)	0.058 (3)	0.057 (2)	−0.014 (2)	0.0059 (19)	0.010 (2)
C7	0.056 (3)	0.062 (3)	0.056 (3)	−0.002 (2)	−0.005 (2)	0.010 (2)
C8	0.078 (3)	0.034 (2)	0.040 (2)	0.001 (2)	0.014 (2)	0.0018 (16)
C9	0.059 (3)	0.050 (2)	0.049 (2)	−0.018 (2)	0.020 (2)	0.0019 (19)
C10	0.042 (2)	0.052 (2)	0.049 (2)	−0.0019 (18)	0.0104 (17)	0.0035 (18)
C11	0.049 (2)	0.038 (2)	0.040 (2)	−0.0029 (17)	0.0022 (16)	0.0068 (16)
C12	0.068 (3)	0.041 (2)	0.051 (2)	0.0125 (19)	0.011 (2)	0.0115 (18)
C13	0.078 (3)	0.049 (2)	0.040 (2)	0.012 (2)	0.009 (2)	0.0093 (18)
C14	0.051 (2)	0.056 (2)	0.043 (2)	0.0058 (19)	−0.0006 (18)	−0.0016 (19)
C15	0.064 (3)	0.072 (3)	0.048 (2)	0.028 (2)	−0.006 (2)	0.006 (2)
C16	0.071 (3)	0.072 (3)	0.034 (2)	0.013 (2)	−0.0016 (19)	0.009 (2)
C17	0.092 (4)	0.073 (3)	0.052 (3)	0.026 (3)	0.012 (2)	0.003 (2)
C18	0.058 (3)	0.080 (3)	0.037 (2)	0.022 (2)	−0.0031 (19)	0.006 (2)
C19	0.074 (3)	0.134 (5)	0.059 (3)	0.015 (3)	0.004 (3)	−0.013 (3)
C20	0.093 (5)	0.231 (10)	0.067 (4)	0.062 (6)	0.018 (4)	−0.017 (6)
C21	0.174 (9)	0.150 (8)	0.073 (5)	0.103 (8)	−0.004 (5)	−0.019 (5)
C22	0.172 (8)	0.086 (4)	0.071 (4)	0.023 (5)	−0.024 (5)	−0.013 (3)
C23	0.088 (4)	0.085 (4)	0.055 (3)	0.011 (3)	−0.011 (3)	0.000 (3)
C24	0.116 (6)	0.157 (7)	0.118 (6)	−0.049 (5)	0.000 (4)	0.011 (5)
Cl1	0.1332 (12)	0.0644 (8)	0.0662 (8)	0.0031 (8)	0.0132 (8)	0.0303 (6)
N1	0.086 (3)	0.061 (2)	0.057 (2)	0.015 (2)	0.024 (2)	0.0205 (18)
O1	0.095 (2)	0.072 (2)	0.0546 (18)	0.0134 (18)	0.0346 (17)	0.0237 (16)
O2	0.073 (2)	0.083 (2)	0.0402 (16)	0.0342 (17)	0.0011 (14)	0.0025 (15)

Geometric parameters (Å, º) top

C1—C2	1.487 (6)	C13—H13	0.9300
C1—H1A	0.9600	C14—O2	1.371 (5)
C1—H1B	0.9600	C14—C15	1.376 (5)
C1—H1C	0.9600	C15—C16	1.369 (6)
C2—C3	1.344 (5)	C15—H15	0.9300
C2—O1	1.351 (5)	C16—H16	0.9300
C3—C4	1.426 (5)	C17—O2	1.439 (5)
C3—C5	1.483 (5)	C17—C18	1.494 (6)
C4—N1	1.317 (5)	C17—H17A	0.9700
C4—C11	1.476 (5)	C17—H17B	0.9700
C5—C10	1.381 (5)	C18—C23	1.368 (7)
C5—C6	1.384 (5)	C18—C19	1.383 (7)
C6—C7	1.375 (5)	C19—C20	1.364 (9)
C6—H6	0.9300	C19—H19	0.9300
C7—C8	1.361 (6)	C20—C21	1.334 (12)
C7—H7	0.9300	C20—H20	0.9300
C8—C9	1.363 (6)	C21—C22	1.361 (11)
C8—Cl1	1.745 (4)	C21—H21	0.9300
C9—C10	1.381 (5)	C22—C23	1.402 (9)
C9—H9	0.9300	C22—H22	0.9300
C10—H10	0.9300	C23—C24	1.493 (8)
C11—C16	1.383 (5)	C24—H24A	0.9600
C11—C12	1.383 (5)	C24—H24B	0.9600
C12—C13	1.384 (5)	C24—H24C	0.9600
C12—H12	0.9300	N1—O1	1.411 (4)
C13—C14	1.373 (5)

C2—C1—H1A	109.5	O2—C14—C13	124.7 (3)
C2—C1—H1B	109.5	O2—C14—C15	115.7 (3)
H1A—C1—H1B	109.5	C13—C14—C15	119.6 (4)
C2—C1—H1C	109.5	C16—C15—C14	120.2 (4)
H1A—C1—H1C	109.5	C16—C15—H15	119.9
H1B—C1—H1C	109.5	C14—C15—H15	119.9
C3—C2—O1	110.0 (4)	C15—C16—C11	121.7 (4)
C3—C2—C1	133.8 (4)	C15—C16—H16	119.1
O1—C2—C1	116.2 (4)	C11—C16—H16	119.1
C2—C3—C4	104.9 (3)	O2—C17—C18	108.0 (3)
C2—C3—C5	125.8 (4)	O2—C17—H17A	110.1
C4—C3—C5	129.2 (3)	C18—C17—H17A	110.1
N1—C4—C3	110.8 (3)	O2—C17—H17B	110.1
N1—C4—C11	118.2 (3)	C18—C17—H17B	110.1
C3—C4—C11	131.0 (3)	H17A—C17—H17B	108.4
C10—C5—C6	118.1 (3)	C23—C18—C19	119.4 (5)
C10—C5—C3	120.9 (3)	C23—C18—C17	121.9 (5)
C6—C5—C3	121.0 (3)	C19—C18—C17	118.6 (5)
C7—C6—C5	121.4 (4)	C20—C19—C18	121.3 (7)
C7—C6—H6	119.3	C20—C19—H19	119.4
C5—C6—H6	119.3	C18—C19—H19	119.4
C8—C7—C6	118.9 (4)	C21—C20—C19	119.9 (8)
C8—C7—H7	120.6	C21—C20—H20	120.0
C6—C7—H7	120.6	C19—C20—H20	120.0
C7—C8—C9	121.5 (4)	C20—C21—C22	120.2 (8)
C7—C8—Cl1	119.4 (3)	C20—C21—H21	119.9
C9—C8—Cl1	119.1 (3)	C22—C21—H21	119.9
C8—C9—C10	119.4 (3)	C21—C22—C23	121.5 (8)
C8—C9—H9	120.3	C21—C22—H22	119.3
C10—C9—H9	120.3	C23—C22—H22	119.3
C9—C10—C5	120.7 (4)	C18—C23—C22	117.7 (6)
C9—C10—H10	119.7	C18—C23—C24	121.5 (6)
C5—C10—H10	119.7	C22—C23—C24	120.8 (7)
C16—C11—C12	117.1 (4)	C23—C24—H24A	109.5
C16—C11—C4	120.2 (3)	C23—C24—H24B	109.5
C12—C11—C4	122.6 (3)	H24A—C24—H24B	109.5
C11—C12—C13	121.8 (4)	C23—C24—H24C	109.5
C11—C12—H12	119.1	H24A—C24—H24C	109.5
C13—C12—H12	119.1	H24B—C24—H24C	109.5
C14—C13—C12	119.5 (4)	C4—N1—O1	105.8 (3)
C14—C13—H13	120.3	C2—O1—N1	108.5 (3)
C12—C13—H13	120.3	C14—O2—C17	117.7 (3)

O1—C2—C3—C4	−0.5 (5)	C12—C13—C14—O2	−177.9 (4)
C1—C2—C3—C4	−179.0 (5)	C12—C13—C14—C15	0.7 (7)
O1—C2—C3—C5	177.6 (3)	O2—C14—C15—C16	178.4 (4)
C1—C2—C3—C5	−0.9 (8)	C13—C14—C15—C16	−0.3 (7)
C2—C3—C4—N1	0.2 (5)	C14—C15—C16—C11	−0.3 (7)
C5—C3—C4—N1	−177.8 (4)	C12—C11—C16—C15	0.5 (6)
C2—C3—C4—C11	−177.8 (4)	C4—C11—C16—C15	−175.9 (4)
C5—C3—C4—C11	4.2 (7)	O2—C17—C18—C23	−77.0 (5)
C2—C3—C5—C10	−115.9 (5)	O2—C17—C18—C19	105.2 (5)
C4—C3—C5—C10	61.7 (5)	C23—C18—C19—C20	−0.3 (8)
C2—C3—C5—C6	63.4 (6)	C17—C18—C19—C20	177.7 (5)
C4—C3—C5—C6	−119.0 (5)	C18—C19—C20—C21	1.3 (10)
C10—C5—C6—C7	−0.9 (6)	C19—C20—C21—C22	−1.1 (12)
C3—C5—C6—C7	179.8 (4)	C20—C21—C22—C23	−0.2 (11)
C5—C6—C7—C8	0.3 (7)	C19—C18—C23—C22	−1.0 (7)
C6—C7—C8—C9	0.6 (6)	C17—C18—C23—C22	−178.8 (4)
C6—C7—C8—Cl1	179.5 (3)	C19—C18—C23—C24	177.7 (5)
C7—C8—C9—C10	−0.8 (6)	C17—C18—C23—C24	−0.1 (7)
Cl1—C8—C9—C10	−179.8 (3)	C21—C22—C23—C18	1.2 (9)
C8—C9—C10—C5	0.2 (6)	C21—C22—C23—C24	−177.5 (6)
C6—C5—C10—C9	0.6 (6)	C3—C4—N1—O1	0.2 (5)
C3—C5—C10—C9	180.0 (3)	C11—C4—N1—O1	178.4 (3)
N1—C4—C11—C16	13.4 (6)	C3—C2—O1—N1	0.6 (5)
C3—C4—C11—C16	−168.7 (4)	C1—C2—O1—N1	179.4 (4)
N1—C4—C11—C12	−162.7 (4)	C4—N1—O1—C2	−0.5 (5)
C3—C4—C11—C12	15.1 (6)	C13—C14—O2—C17	−0.5 (6)
C16—C11—C12—C13	0.0 (6)	C15—C14—O2—C17	−179.2 (4)
C4—C11—C12—C13	176.2 (4)	C18—C17—O2—C14	166.7 (4)
C11—C12—C13—C14	−0.5 (7)

Hydrogen-bond geometry (Å, º) top

Cg1, Cg2 and Cg3 are the centroids of the O1/N1/C2–C4, C5–C10 and C11–C16 rings, respectively.

D—H···A	D—H	H···A	D···A	D—H···A
C17—H17A···N1ⁱ	0.97	2.68	3.395 (6)	131
C6—H6···Cg3ⁱⁱ	0.93	2.86	3.747 (5)	159
C19—H19···Cg1ⁱⁱⁱ	0.93	2.77	3.614 (6)	151
C8—Cl1···Cg2^iv	1.75 (1)	3.37 (1)	5.034 (4)	159 (1)

Symmetry codes: (i) x, y, z+1; (ii) −x+2, −y+1, −z+1; (iii) −x+1, −y+1, −z+1; (iv) x, −y−1/2, z−1/2.

Summary of selected van der Waals contacts (Å) involving H atoms in the title compound top

Contact	Distance	Symmetry operation
Cl1···H1C	3.04	x, 1/2 - y, 1/2 + z
N1···H17A	2.68	x, y, -1 + z
H1A···O1	2.74	2 - x, 1 - y, -z
H10···O2	2.72	1 - x, 1 - y, 1 - z
H6···C11	2.80	2 - x, 1 - y, 1 - z
H9···C21	2.94	1 - x, -1/2 + y, 3/2 - z
H20···C9	3.05	1 - x, 1 - y, 2 - z
H22···H24C	2.48	x, 1/2 - y, - 1/2 + z

Percentage contributions of interatomic contacts to the Hirshfeld surface of the title compound top

Contact	Percentage contribution
H···H	48.7
H···C/C···H	22.2
Cl···H/H···Cl	8.8
H···O/O···H	8.2
H···N/N···H	5.1
Cl···C/C···Cl	3.9
C···C	2.1
C···N/N···C	0.4
O···O	0.4
C···O/O···C	0.2

Acknowledgements

The authors acknowledge the Aksaray University, Science and Technology Application and Research Center, Aksaray, Turkey, for the use of the Bruker SMART BREEZE CCD diffractometer (purchased under grant No. 2010 K120480 of the State of Planning Organization). The title compound was produced within the context of a research project supported by the Scientific and Technological Research Council of Turkey (TUBITAK #215S015).

References

Ahmad, K., Khan, M. K., Baig, M. H., Imran, M. & Gupta, G. K. (2018). Anticancer Agents Med. Chem. 18, 46–56. Web of Science CrossRef CAS PubMed Google Scholar
Aitipamula, S. & Vangala, V. R. (2017). J. Indian Inst. Sci. 97, 227–243. Web of Science CrossRef Google Scholar
Banoglu, E., Çelikoğlu, E., Völker, S., Olgaç, A., Gerstmeier, J., Garscha, U., Çalışkan, B., Schubert, U. S., Carotti, A., Macchiarulo, A. & Werz, O. (2016). Eur. J. Med. Chem. 113, 1–10. Web of Science CrossRef CAS PubMed Google Scholar
Barmade, M. A., Murumkar, P. R., Sharma, M. K. & Yadav, M. R. (2016). Curr. Top. Med. Chem. 16, 2863–2883. Web of Science CAS PubMed Google Scholar
Bruker (2007). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Çalışkan, B., Luderer, S., Özkan, Y., Werz, O. & Banoglu, E. (2011). Eur. J. Med. Chem. 46, 5021–5033. Web of Science PubMed Google Scholar
Dündar, Y., Ünlü, S., Banoğlu, E., Entrena, A., Costantino, G., Nunez, M. T., Ledo, F., Şahin, M. F. & Noyanalpan, N. (2009). Eur. J. Med. Chem. 44, 4785–4785. Google Scholar
Efimov, I., Slepukhin, P. & Bakulev, V. (2015). Acta Cryst. E71, o1028. Web of Science CSD CrossRef IUCr Journals Google Scholar
Eren, G., Ünlü, S., Nuñez, M., Labeaga, L., Ledo, F., Entrena, A., Banoğlu, E., Costantino, G. & Şahin, M. F. (2010). Bioorg. Med. Chem. 18, 6367–6376. Web of Science CrossRef CAS PubMed Google Scholar
Ergun, B. C., Nunez, M. T., Labeaga, L., Ledo, F., Darlington, J., Bain, G., Cakir, B. & Banoglu, E. (2010). Arzneim. Forsch. 60, 497–505. CAS Google Scholar
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854. Web of Science CrossRef CAS IUCr Journals Google Scholar
Garscha, U., Voelker, S., Pace, S., Gerstmeier, J., Emini, B., Liening, S., Rossi, A., Weinigel, C., Rummler, S., Schubert, U. S., Scriba, G. K., Çelikoğlu, E., Çalışkan, B., Banoglu, E., Sautebin, L. & Werz, O. (2016). Biochem. Pharmacol. 119, 17–26. Web of Science CrossRef CAS PubMed Google Scholar
Hathwar, V. R., Sist, M., Jørgensen, M. R. V., Mamakhel, A. H., Wang, X., Hoffmann, C. M., Sugimoto, K., Overgaard, J. & Iversen, B. B. (2015). IUCrJ, 2, 563–574. Web of Science CSD CrossRef CAS PubMed IUCr Journals Google Scholar
Hirshfeld, H. L. (1977). Theor. Chim. Acta, 44, 129–138. CrossRef CAS Web of Science Google Scholar
Levent, S., Çalışkan, B., Çiftçi, M., Özkan, Y., Yenicesu, I., Ünver, H. & Banoglu, E. (2013). Eur. J. Med. Chem. 64, 42–53. Web of Science CrossRef CAS PubMed Google Scholar
Murumkar, P. R. & Ghuge, R. B. (2018). Vicinal Diaryl Oxadiazoles, Oxazoles and Isoxazoles, In Vicinal Diaryl Substituted Heterocycles, edited by M. R. Yadav, P. R. Murumkar & R. B. Ghuge, pp. 277–303. Oxford: Elsevier. Google Scholar
Pirol, Ş. C., Çalışkan, B., Durmaz, I., Atalay, R. & Banoglu, E. (2014). Eur. J. Med. Chem. 87, 140–149. Web of Science PubMed Google Scholar
Rohl, A. L., Moret, M., Kaminsky, W., Claborn, K., McKinnon, J. J. & Kahr, B. (2008). Cryst. Growth Des. 8, 4517–4525. Web of Science CSD CrossRef CAS Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Spackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19–32. Web of Science CrossRef CAS Google Scholar
Spek, A. L. (2020). Acta Cryst. E76, 1–11. Web of Science CrossRef IUCr Journals Google Scholar
Turner, M. J., MacKinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). Crystal Explorer17.5. University of Western Australia. Google Scholar
Ünlü, S., Banoglu, E., Ito, S., Niiya, T., Eren, G., Ökçelik, B. & Şahin, M. F. (2007). J. Enzyme Inhib. Med. Chem. 22, 351–361. Web of Science PubMed Google Scholar
Wang, D.-C., Huang, L.-C., Liu, H.-Q., Peng, Y.-R. & Song, J.-S. (2011). Acta Cryst. E67, o3207. Web of Science CSD CrossRef IUCr Journals Google Scholar
Wouters, C. & Ooms, F. (2001). Curr. Pharm. Des. 7, 529–545. Web of Science CrossRef PubMed CAS Google Scholar
Yu, J.-G., Zhu, H.-X., Qiu, J.-K., Wang, D.-C. & Xu, H. (2012). Acta Cryst. E68, o2325. CSD CrossRef IUCr Journals Google Scholar
Zaini, M. F., Razak, I. A., Anis, M. Z. & Arshad, S. (2019). Acta Cryst. E75, 58–63. Web of Science CSD CrossRef IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.